Abstract
Gamma-interferon-inducible lysosomal thiolreductase (GILT) promotes major histocompatibility complex (MHC) class II-restricted presentation of exogenous antigens containing disulfide bonds. Here, we show that GILT also facilitates MHC class I-restricted recognition of such antigens by CD8+ T cells, or cross-presentation. GILT is essential for cross-presentation of a CD8+ T cell epitope of glycoprotein B (gB) from herpes simplex virus 1 (HSV-1) but not for its presentation by infected cells. Initiation of the gB-specific CD8+ T cell response during HSV-1 infection, or cross-priming, is highly GILT-dependent, as is initiation of the response to the envelope glycoproteins of influenza A virus. Efficient cross-presentation of disulfide-rich antigens requires a complex pathway involving GILT-mediated reduction, unfolding, and partial proteolysis, followed by translocation into the cytosol for proteasomal processing.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / metabolism
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Animals
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Antigen Presentation
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Antigens, Viral / immunology*
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CD8-Positive T-Lymphocytes / immunology
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Cross-Priming*
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Cytosol / metabolism
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Dendritic Cells / immunology
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Epitopes, T-Lymphocyte / immunology
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H-2 Antigens / immunology
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HeLa Cells
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Herpes Simplex / immunology*
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Herpes Simplex / metabolism
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Herpesvirus 1, Human / immunology*
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Humans
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Influenza A virus / immunology
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Mice
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Orthomyxoviridae Infections / immunology
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Oxidoreductases / genetics
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Oxidoreductases / metabolism*
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Oxidoreductases Acting on Sulfur Group Donors
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Proteasome Endopeptidase Complex / metabolism
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Viral Envelope Proteins / immunology*
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Viral Envelope Proteins / metabolism*
Substances
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ATP-Binding Cassette Transporters
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Antigens, Viral
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Epitopes, T-Lymphocyte
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H-2 Antigens
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H-2Kb protein, mouse
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Viral Envelope Proteins
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glycoprotein B, Simplexvirus
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transporter associated with antigen processing (TAP)
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Oxidoreductases
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Ifi30 protein, mouse
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Oxidoreductases Acting on Sulfur Group Donors
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Proteasome Endopeptidase Complex